Evidence of selection for an accessible nucleosomal array in humanReport as inadecuate




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BMC Genomics

, 17:526

Comparative and evolutionary genomics

Abstract

BackgroundRecently, a physical model of nucleosome formation based on sequence-dependent bending properties of the DNA double-helix has been used to reveal some enrichment of nucleosome-inhibiting energy barriers NIEBs nearby ubiquitous human -master- replication origins. Here we use this model to predict the existence of about 1.6 millions NIEBs over the 22 human autosomes.

ResultsWe show that these high energy barriers of mean size 153 bp correspond to nucleosome-depleted regions NDRs in vitro, as expected, but also in vivo. On either side of these NIEBs, we observe, in vivo and in vitro, a similar compacted nucleosome ordering, suggesting an absence of chromatin remodeling. This nucleosomal ordering strongly correlates with oscillations of the GC content as well as with the interspecies and intraspecies mutation profiles along these regions. Comparison of these divergence rates reveals the existence of both positive and negative selections linked to nucleosome positioning around these intrinsic NDRs. Overall, these NIEBs and neighboring nucleosomes cover 37.5 % of the human genome where nucleosome occupancy is stably encoded in the DNA sequence. These 1 kb-sized regions of intrinsic nucleosome positioning are equally found in GC-rich and GC-poor isochores, in early and late replicating regions, in intergenic and genic regions but not at gene promoters.

ConclusionThe source of selection pressure on the NIEBs has yet to be resolved in future work. One possible scenario is that these widely distributed chromatin patterns have been selected in human to impair the condensation of the nucleosomal array into the 30 nm chromatin fiber, so as to facilitate the epigenetic regulation of nuclear functions in a cell-type-specific manner.

KeywordsNucleosome depleted regions Sequence evolution Nucleosome ordering Mutation rates GC content Human genome Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-2880-2 contains supplementary material, which is available to authorized users.

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Author: Guénola Drillon - Benjamin Audit - Françoise Argoul - Alain Arneodo

Source: https://link.springer.com/







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